Cognitive functions and brain cell activities show responses to estrogens that give a general basis for the protective effects of estrogen replacement therapy (ERT) in Alzheimer disease (AD). A team of USC investigators proposes experiments on rodent models in vivo and in vitro to analyze mechanisms by which estrogens interact with neurons and glia to modify synaptic plasticity. We will test the hypothesis that estrogens are neuroprotective by examining molecular, cellular, and physiological responses to estrogen and interactions with lesions in rats as a function of aging. We also examine bioactivities of equine estrogens that are constituents of Premarin, the most widely used ERT.